EP-A-0 678 503 describes delta-amino-gamma-hydroxy-omega-aryl-alkanecarboxamides which have renin-inhibiting properties and can be used as antihypertensives in pharmaceutical formulations. The preparation processes described there are unsuitable for an industrial process, especially with regard to the sometimes unsatisfactory yields and number of reaction steps. A great disadvantage of the processes described there is that the total yield of pure diastereomers is too low.
An improved preparation process for delta-amino-gamma-hydroxy-omega-aryl-alkanecarboxamides has been described in WO 2002/02487 A1. In the process described there, arylaldehydes are reacted with 2-alkylacetic esters to give 3-hydroxy-2-alkyl-3-arylpropionic esters, from which conversion of the alcohol function to a leaving group followed by elimination affords 2-alkyl-3-arylacrylic esters, which are reduced to (E)-2-alkyl-3-arylprop-2-en-1-ols, which are then hydrogenated by asymmetric hydrogenation with high stereoselectivity to chiral 2-methyl-3-phenyl-propan-1-ols. The chiral 2-methyl-3-phenylpropan-1-ols are subsequently converted by hydrogenation to (3-halo-2-alkylpropyl)aryl compounds, which are reacted with chiral (E)-5-halo-2-alkylpent-4-enamides to give 2,7-dialkyl-8-aryl-4-octenoylamides. The double bond of the 2,7-dialkyl-8-aryl-4-octenoylamides is subsequently halogenated simultaneously in the 5-position and hydroxylated with lactonization in the 4-position, then the halide is replaced with azide, the lactone is amidated and then the azide is converted to the amine group. The desired alkanecarboxamides are obtained in significantly higher overall yields in this process compared to the process published in EP-A-0 678 503, although the high number of process stages is disadvantageous.